This Administrative Core will serve to coordinate the efforts ofthe three Projects and oversee the utilization of the Core Facilities to ensure that the goals of this Project are met. This Core will be located at the University of Chicago. The Program Director is Dr. Elizabeth McNally, a physician scientist at the University of Chicago who is an expert in mouse modeling of muscular dystrophy. Dr. McNally also provides care to patients with muscular dystrophy in the clinic she directs. Dr. McNally will direct Project 1 and lead this Administrative Core A. The Project leaders are Dr. Se-Jin Lee, a Professor at Johns Hopkins, and Dr. Jeffrey Molkentin, a Professor at the University of Cincinnati. Each of these investigators brings unique expertise and commitment to the study of muscular dystrophy. Dr. McNally has generated animal models of muscular dystrophy and identified the modifier gene Ltbp4. Dr. Lee discovered the myostatin pathway and its ability to regulate muscle growth. Dr. Molkentin is expert in generating mouse models with cardiac and muscle disease and has a longstanding interest in fibrosis. These three investigators have common interests, supported by collaboration, and are uniquely positioned to identify pathways and develop and test new therapies for muscular dystrophy. The outcomes from this Program will be: 1) Identify extracellular and intracellular events that regulate TGFB and myostatin processing and availability. 2) Discover the relationship between muscle growth and muscle fibrosis mediated through TGFB and myostatin. 3) Realize new targets for therapy development including protease inhibitors, soluble receptors, decoy myostatin molecules and drugs to inhibit intracellular signaling pathways. To take advantage ofthe strengths ofthe three laboratories and three institutions requires regular communication, including videoconferencing, and face to face meetings throughout the year. Core A will coordinate communication, maintain and distribute up to date protocols, review Core utilization, oversee Project progress and coordinate review by the Internal and External Advisory Boards.